title: Reduced CCK signaling in obese-prone rats fed a high fat diet.
abstract: Deficits in satiation signaling during obesogenic feeding have been proposed to play a role in hyperphagia and weight gain in animals prone to become obese. However, whether this impaired signaling is due to high fat (HF) feeding or to their obese phenotype is still unknown. Therefore, in the current study, we examined the effects of CCK-8 (0.5, 1.0, 2.0, and 4.0 μg/kg) on suppression of food intake of HF-fed obese prone (OP) and resistant (OR) rats. Additionally, we determined the role of endogenous CCK in lipid-induced satiation by measuring plasma CCK levels following a lipid gavage, and tested the effect of pretreatment with devazepide, a CCK-1R antagonist on intragastric lipid-induced satiation. Finally, we examined CCK-1R mRNA levels in the nodose ganglia. We show that OP rats have reduced feeding responses to the low doses of exogenous CCK-8 compared to OR rats. Furthermore, OP rats exhibit deficits in endogenous CCK signaling, as pretreatment with devazepide failed to abolish the reduction in food intake following lipid gavage. These effects were associated with reduced plasma CCK after intragastric lipid in OP but not OR rats. Furthermore, HF feeding resulted in downregulation of CCK-1Rs in the nodose ganglia of OP rats. Collectively, these results demonstrate that HF feeding leads to impairments in lipid-induced CCK satiation signaling in obese-prone rats, potentially contributing to hyperphagia and weight gain.
authors.affiliation: UMR1913-MICALIS, INRA, Domaine de Vilvert, Jouy-en-Josas 78352, France; UMR1913-MICALIS, AgroParisTech, Domaine de Vilvert, Jouy-en-Josas, 78352, France; Doctoral School of Physiology and Pathophysiology, University Pierre and Marie Currie, 15 rue de l'Ecole de Médecine, Paris 75006, France.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Duca
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
authors.forename: Mihai
authors.initials: M
authors.lastname: Covasa
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020109:Devazepide / Q000494:pharmacology; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology
chemical_list: D004041:Dietary Fats; D006727:Hormone Antagonists; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide
keywords: CCK-1R; DIO; Devazepide; High-fat diet; Obesity